AZ, MZ, and the Pulmonary System Response to Hypoxia

University of British Columbia

Status and phase: Completed; Phase 4

Conditions: Altitude Sickness; Hypertension, Pulmonary

Treatments: Drug: Acetazolamide; Drug: Placebo; Drug: Methazolamide

Study type: Interventional

Funder types: Other

Identifiers

NCT02760121

H16-00028

Details and patient eligibility

About

The purpose of this proposal is to compare the physiological effects of acetazolamide (AZ) and methazolamide (MZ) on the control of breathing and hypoxic pulmonary vasoconstriction. The first objective is to assess the effects of AZ and MZ on the control of breathing in normoxia and hypoxia. To achieve this the ventilatory interaction between oxygen and carbon dioxide will be measured and effects compared between placebo, AZ, and MZ conditions. In addition, the isocapnic and poikilocapnic hypoxic ventilatory response and hypercapnic ventilatory response will be measured with each drug. The second objective is to assess the effects of AZ and MZ on the control of the pulmonary vasculature during hypoxia. Pulmonary pressure and cardiac output will be measured during 60 minutes of poikilocapnic hypoxia.

Enrollment: 14 patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 18-40 years of age
• regularly physically active
• male

Exclusion criteria

• ex-smokers
• pulmonary function <80% of predicted
• contraindications to carbonic anhydrase inhibitors (eg. severe or absolute glaucoma, adrenocortical insufficiency, hepatic insufficiency, renal insufficiency, sulfa allergy or an electrolyte imbalance such as hyperchloremic acidosis)
• Obese (BMI>30Kg/m2)
• diuretic medication use
• blood thinner use
• anti-platelet drug use.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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14 participants in 3 patient groups, including a placebo group

Acetazolamide

Experimental group

Description:

Participants will be dosed 250mg Acetazolamide (p.o.) three times per day for two days prior to and a single dose on the day of study.

Treatment:

Drug: Acetazolamide

Methazolamide

Experimental group

Description:

Participants will be dosed 100mg Methazolamide (p.o.) twice daily separated by a placebo for two days prior to and a single dose on the day of study. The placebo dose is provided to match the dosing schedule between conditions.

Treatment:

Drug: Methazolamide

Placebo

Placebo Comparator group

Description:

Participants will take (p.o.) placebo pills three times per day for two days prior to and a single dose on the day of study.

Treatment:

Drug: Placebo